Non-functional DNA: quantity.

by T. Ryan Gregory, on February 11th, 2008

In my previous post, I noted that because of what we understand about the nature, origins, and cross-taxon quantitative diversity of the various sorts of non-genic DNA in large eukaryote genomes, the default assumption is that much or even most of it is not functional at the cell and organism levels. Thus, the burden of proof rests with authors who claim that a large fraction, or indeed most or all, of this DNA is functional for the organisms in which it occurs.

This should not be construed as claiming that all non-genic DNA is assumed to be non-functional. I have pointed out in various preceding posts that even those who postulated non-adaptive explanations for its existence did not rule out — and indeed, explicitly favoured — the notion that a significant portion would turn out to serve a function. You need not take my word for this, as it is not difficult to find unambiguous statements from the original authors themselves.

For example, here are Orgel and Crick (1980) who, along with Doolittle and Sapienza (1980), first proposed the concept of “selfish DNA” in detail:

It would be surprising if the host genome did not occasionally find some use for particular selfish DNA sequences, especially if there were many different sequences widely distributed over the chromosomes.One obvious use … would be for control purposes at one level or another.

Here, too, is Comings (1972), the first person to use the term “junk DNA” in print and the first to provide a substantive discussion of the topic. (The term was coined by Ohno in 1972, but Comings’s paper appeared in print first, citing Ohno as ‘in press’, and Ohno used the term only in the title).

These considerations suggest that up to 20% of the genome is actively used and the remaining 80+% is junk. But being junk doesn’t mean it is entirely useless. Common sense suggests that anything that is completely useless would be discarded. There are several possible functions for junk DNA.

The use of the terms “selfish DNA” or “junk DNA” has changed over time, and both are now often applied to all non-genic DNA, rather than to the sequences to which they originally referred (i.e., transposable elements and pseudogenes, respectively). Moreover, it seems that many authors — at least those whose studies focus primarily on protein-coding genes and DNA sequencing — believe that the assumption has been that all non-genic DNA is “junk” in the sense of totally non-functional. However, amidst any such assumptions there has always been a diversity of views on the subject, ranging from assuming that most non-genic DNA is non-functional (as in the quotes above) to expecting it all to be functional — the latter being a position held by strict adaptationists, and a large part of the motivation for proposing the alternative view of selfish DNA the first place.

As with many issues in evolution, this is a matter of relative quantity, not an exclusive dichotomy. We may reasonably expect a significant fraction of non-genic DNA to show evidence of function, and the pursuit of such evidence is a valid and important endeavour. It does not follow, however, that the pendulum must be perceived to swing from entirely functional to entirely non-functional and back again. We will undoubtedly refine our estimates of the amount of non-genic DNA that is mutualistic at the organism level, how much is commensal, and how much is best characterized as parasitic in nature.

As it stands, the evidence suggests that about 5% of the human genome is functional at the organism level. The total may be higher — as noted, Comings suggested 20% is actively utilized. It is conceivable that 50% or more of the genome is functional, perhaps in structural roles or some other higher-order capacity. It would require evidence to support this contention, however, and the question would remain as to why an onion requires 5x more of this structural or otherwise essential DNA, and why some of its close relatives can get by with half as much while others have twice the onion amount. There is nothing remarkable about onions in this sense, by the way — animal genome sizes alone cover a more than 7,000-fold range, and even among vertebrates there is a 350-fold difference. The range among single-celled protozoa is at least 30,000-fold, though even higher estimates have been presented.

The take home message is simply this. What we know about eukaryote genomes suggests that there are many mechanisms that can add non-coding DNA that do not require it to be functional. This does not in any way preclude the possibility of, or invalidate the search for, function in some, many, or possibly even most of those non-coding components. How much proves to be functional is an empirical question, and at present the indication seems to be that most non-genic DNA is non-functional. That said, non-functional is not the same as inconsequential.

I am curious about your comment about an onion needing so much more “junk” DNA in a structural role. Might it be simpler, that the onion is just an onion and happens to have this large portion of “junk”. I may also be that this large portion of “junk” was part of a successful genome. There may be many other possible ways the onion genome might be successful (with less or more junk), this is just the one that arose.

I am curious about your comment about an onion needing so much more “junk” DNA in a structural role.

I do not claim that the onion requires 5x more DNA. I am noting that if someone else wishes to claim that all non-coding DNA is essential, then they would have to account for why an onion needs so much more of it. This is just one example — it’s nothing special or negative about onions.

Enjoying the site – thanks for the effort involved. It occurred to me (an engineer with some limited life-science training at post-grad level) that we might assume we started out somewhere (say pre-Cambrian) with a perfect DNA sequence – all of it (every haploid pair) functional, but only part expressed as normal genes. Over time, the various mechanism for altering how much DNA is retained and is useful will add some (duplication), delete some (non-functional, or redundant bits only – obviously), and some might be inserted via viral-like symbiosis – whatever the process, the situation will become confused after several hundred million years. Slowly but surely, some things, like onions (if you say so – I have no idea), might foolishly and up with piles of this real junk hanging around – accidents happen after all during procreation (sexual or otherwise) and yet cell division is extremely conservative. So, some lucky organisms will (by chance alone) keep their DNA tight and slick – but this may come at a cost – less ability to adapt. Like me carrying around a welder that I haven’t used in years – just in case – carrying spare DNA might come in handy. Who knows, those sneaky onions might just be waiting for the right moment to morph into Triffids! Just a thought…